Lipid peroxidation and total antioxidant capacity in vitreous, aqueous humor, and blood samples from patients with diabetic retinopathy

PurposeTo evaluate levels of malondialdehyde and the total antioxidant capacity (TAC) in the blood, aqueous humor, and vitreous bodies of diabetic and nondiabetic patients. We also measured the blood energy charge potential (ECP).MethodsWe examined 19 patients with type 2 diabetes mellitus and diabetic retinopathy. Ten were scheduled for cataract surgery and pars plana vitrectomy because of proliferative diabetic retinopathy (PDR). The other nine, with mild nonproliferative PDR (NPDR), and fourteen nondiabetic, age-matched subjects enrolled as a control group were scheduled for cataract surgery and vitrectomy because of epiretinal membranes. Blood, aqueous humor and vitreous body samples were collected at the time of surgery. Malondialdehyde concentrations and blood ECP were measured with high-performance liquid chromatography. The TAC of the samples was estimated with the oxygen radical absorbance capacity method.ResultsThe level of blood and vitreous malondialdehyde in the PDR group was significantly higher compared to controls and to NPDR patients. PDR patients also had lower levels of TAC at the vitreous body and aqueous humor level, but not at the blood level, compared to controls and with NPDR patients. In all diabetic patients, the blood ECP values were significantly lower, compared to control subjects.ConclusionsOur data support the hypothesis that oxidative stress and the decrease of antioxidant defenses are associated with the progression of diabetic retinopathy to its proliferative form. Antioxidant supply may have the effect of correcting oxidative stress and inhibiting disease progression

ACE2 expression is related to the interferon response in airway epithelial cells but is that functional for SARS-CoV-2 entry?

In vitro interferon (IFN)α treatment of primary human upper airway basal cells has been shown to drive ACE2 expression, the receptor of SARS-CoV-2. The protease furin is also involved in mediating SARS‐CoV‐2 and other viral infections, although its association with early IFN response has not been evaluated yet. In order to assess the in vivo relationship between ACE2 and furin expression and the IFN response in nasopharyngeal cells, we first examined ACE2 and furin levels and their correlation with the well-known marker of IFNs’ activation, ISG15, in children (n = 59) and adults (n = 48), during respiratory diseases not caused by SARS-CoV-2. A strong positive correlation was found between ACE2 expression, but not of furin, and ISG15 in all patients analyzed. In addition, type I and III IFN stimulation experiments were performed to examine the IFN-mediated activation of ACE2 isoforms (full-length and truncated) and furin in epithelial cell lines. Following all the IFNs treatments, only the truncated ACE2 levels, were upregulated significantly in the A549 and Calu3 cells, in particular by type I IFNs. If confirmed in vivo following IFNs’ activation, the induction of the truncated ACE2 isoform only would not enhance the risk of SARS‐CoV‐2 infection in the respiratory tract

Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults

BACKGROUND: Outcomes in patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) have improved with the use of tyrosine kinase inhibitors. Molecular remission is a primary goal of treatment.METHODS: We conducted a phase 2 single-group trial of first-line therapy in adults with newly diagnosed Ph-positive ALL (with no upper age limit). Dasatinib plus glucocorticoids were administered, followed by two cycles of blinatumomab. The primary end point was a sustained molecular response in the bone marrow after this treatment.RESULTS: Of the 63 patients (median age, 54 years; range, 24 to 82) who were enrolled, a complete remission was observed in 98%. At the end of dasatinib induction therapy (day 85), 29% of the patients had a molecular response, and this percentage increased to 60% after two cycles of blinatumomab; the percentage of patients with a molecular response increased further after additional blinatumomab cycles. At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients who had an IKZF1 deletion plus additional genetic aberrations (CDKN2A or CDKN2B, PAX5, or both [i.e., IKZF1 plus]). ABL1 mutations were detected in 6 patients who had increased minimal residual disease during induction therapy, and all these mutations were cleared by blinatumomab. Six relapses occurred. Overall, 21 adverse events of grade 3 or higher were recorded. A total of 24 patients received a stem-cell allograft, and 1 death was related to transplantation (4%).CONCLUSIONS: A chemotherapy-free induction and consolidation first-line treatment with dasatinib and blinatumomab that was based on a targeted and immunotherapeutic strategy was associated with high incidences of molecular response and survival and few toxic effects of grade 3 or higher in adults with Ph-positive ALL. (Funded by Associazione Italiana per la Ricerca sul Cancro and others; GIMEMA LAL2116 D-ALBA EudraCT number, 2016-001083-11; ClinicalTrials.gov number, NCT02744768.)

An Italian Multicenter Study on the Epidemiology of Respiratory Syncytial Virus During SARS-CoV-2 Pandemic in Hospitalized Children

Since the beginning of 2020, a remarkably low incidence of respiratory virus hospitalizations has been reported worldwide. We prospectively evaluated 587 children, aged <12 years, admitted for respiratory tract infections from 1 September 2021 to 15 March 2022 in four Italian pediatric hospitals to assess the burden of respiratory viruses during the COVID-19 pandemic in Italy. At admission, a Clinical Respiratory Score was assigned and nasopharyngeal or nasal washing samples were collected and tested for respiratory viruses. Total admissions increased from the second half of October 2021 to the first half of December 2021 with a peak in early November 2021. The respiratory syncytial virus (RSV) incidence curve coincided with the total hospitalizations curve, occurred earlier than in the pre-pandemic years, and showed an opposite trend with respect to the incidence rate of SARS-CoV-2. Our results demonstrated an early peak in pediatric hospitalizations for RSV. SARS-CoV-2 may exhibit a competitive pressure on other respiratory viruses, most notably RSV

Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target

© 2009 Albini et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection

Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen-specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases

An Italian Pattern of Social Enterprise: the Social Cooperative

The article describes how the social cooperative has become instrumental in the expansion of the social economy in Italy. It reports the contribution these associations have made to broadening the concept and parameters of volunteer organizations, providing basic social welfare services and integrating many disadvantaged people into the active society. By virtue of their ability to activate wider social projects, this type of social enterprise could be of interest and relevance to other countries (following this example, in 2001 the French government created the Sociétés coopératives d’intérét collectif), but they call for adequate competencies and protection under specific laws because, on the whole, they are too small and depended on public contributions

The relationship between entrepreneurial characteristics, firms’ positioning and local development. An empirical survey

The paper aims to explain how the presence of entrepreneurs’ specific subjective characteristics can influence a firm’s strategic orientation and, as a consequence, local development. By analyzing several subjective characteristics taken from a sample of 101 successful entrepreneurs from Southern Italy, certain issues emerge regarding the link between the economic performance of the ventures launched in this area and the weak level of growth. The research approach makes use of the Global Entrepreneurship Monitor conceptual model which summarizes the major causal mechanisms affecting national economic growth

Nuclear factor-kappaB and tumor-associated macrophages.

International audienceTumor-associated macrophages (TAM) have been linked with the progression of cancer by favoring tumor angiogenesis, growth, and metastasis. The precise mechanisms that maintain the protumor phenotype of TAM are poorly understood, but recent research has highlighted a number of signaling pathways that are important in TAM phenotype and function. Nuclear factor-kappaB (NF-kappaB) is considered the master regulator of inflammatory and immune responses. Recently several genetic studies have indicated NF-kappaB is an important pathway in TAM for the integration of signals from the tumor microenvironment that promote carcinogenesis. This review will focus on the role of NF-kappaB in TAM and the potential of targeting this pathway as a novel therapeutic strategy against cancer